TM4SF5
protein-codingtransmembrane 4 L six family member 5
Gene summary
The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein and is highly similar in sequence and structure to transmembrane 4 superfamily member 1. It may play a role in cell proliferation, and overexpression of this protein may be associated with the uncontrolled growth of tumour cells. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TM4SF5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003963.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 23 | 1 | 24 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 26 | 1 | 0 | 27 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003954.2 | 5 | MANE Select | |
| Ensembl | ENSP00000270560.3 | 5 | MANE Select | |
| Ensembl | ENSP00000531333.1 | 4 | Standard | |
| Ensembl | ENSP00000531333.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tm4sf5 | Danio rerio | Structure: fast muscle cell Quality: mislocalised abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Cellular Component
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000270560
- Coding exons
- 5
- Length
- 11328
- Individuals with no LoFs
- 125698
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 50
- Defined
- 125748
- p
- 0.000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.795 | 108 | 134 | 0.807 | 0.00000857 | 1251 |
| Missense (PolyPhen) | 51 | 57.016 | 0.89449 | 579 | ||
| Synonymous | 0.522 | 54 | 59.1 | 0.914 | 0.00000415 | 431 |
| Loss of Function | 1.64 | 5 | 10.8 | 0.461 | 6.47e-7 | 103 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00054 | 0.00054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00030 | 0.00029 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.133
Intolerance Scores
- LoFtool
- 0.682
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 49.76
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.108
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |